Untargeted Urinary Proteomics Uncovers Nephroprotective and Systemic Adaptations after Obesity Surgery-Induced Weight Loss

Weight
loss induced by bariatric surgery (BS) has a profound impact
on several biological systems. This study aimed to identify urinary
proteins reflecting kidney and systemic adaptations to weight loss
in patients with obesity before and after BS. Urine samples from individuals
with obesity (n = 16) were collected before and two
years after BS. Untargeted high-resolution LC-MS with label-free quantification
was used to assess urinary proteome changes. Among the 2347 identified
proteins, 1016 depicted a significantly different abundance postsurgery
(p < 0.05). In particular, 54 proteins were either
upregulated (n = 42) or downregulated (n = 12) by at least 50% (≥1.5-fold). Protein functional classification
revealed associations with immune function (n = 17;
e.g., protein S100-A9, α-1-acid glycoproteins); cytoskeleton/cell
adhesion (n = 11; e.g., supervillin, ezrin, periplakin),
and kidney adaptation (n = 11; e.g., elongation factor
1-α 1, megalin, cubilin). A decrease in inflammation protein
markers (α-1-acid glycoproteins), alongside an increase in proteins
associated with immune modulation and oxidative stress protection
(dipeptidase 1, heat shock cognate 71 kDa protein) were observed.
Overall, the urinary proteome suggests changes in inflammation and
oxidative stress status, as well as in kidney function and cellular
organization succeeding BS. Our results reveal potential novel pathways
contributing to systemic modifications and nephroprotective effects
of BS-induced weight loss.